Okayama University Medical SchoolActa Medica Okayama0386-300X6812014Long-term Observation of Osteomalacia Caused by Adefovir-Induced Fanconifs Syndrome5356ENTomohiroTerasakaEijiroUetaHirotakaEbaraKoichiWasedaYoshihisaHanayamaAkinobuTakakiTomokoKawabataHitoshiSugiyamaKoHidanFumioOtsukaCase Report10.18926/AMO/52145A 64-year-old man suffering polyarthralgia and bone pain was referred to our hospital. Renal dysfunction,
hypophosphatemia and increased levels of bone alkaline phosphatase were found. The patientʼs serum creatinine level had gradually increased after the initiation of adefovir dipivoxil administration for hepatitis B. In agreement with multifocal uptakes of bone scintigraphy, iliac bone biopsy revealed an abnormal increase in osteoid tissues. Reducing the dose of adefovir and initiating the administration of eldecalcitol were effective for reducing proteinuria and glucosuria, and for ameliorating bone pain with an increase in serum phosphate level. This case first showed a clinical course of hypophosphatemic osteomalacia caused by secondary Fanconiʼs syndrome for 8 years after adefovir administration. Early diagnosis is important for the reversibility of bone damage and for a better renal prognosis.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7032016Increased Serum KL-6 Levels Induced by Pulmonary Mycobacterium Avium Complex Infection in a Patient with RA-associated Lung Disease217221ENKoichiWasedaDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazukiOchoDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKouHasegawaDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKosukeKimuraDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayaIwamuroDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshihisaHanayamaDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEiseiKondoDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartments of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumioOtsukaDepartments of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCase Report10.18926/AMO/54422KL-6 is a glycoprotein found predominantly on type II pneumocytes and alveolar macrophages, and often shows increased serum levels in patients with interstitial pneumonia. We report a case of mycobacterium avium complex (MAC) infection whose disease activity was correlated with KL-6 levels in serum. During treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) with prednisolone, chest image findings improved in association with decreased KL-6 levels. Following tapering of prednisolone, chest image findings deteriorated again as levels of KL-6 increased, suggesting recurrence of RA-ILD. Bronchoscopic examination revealed active MAC infection. Treatment of MAC infection not only improved chest image findings but also decreased KL-6 levels in serum, suggesting that KL-6 was increased by active MAC infection by itself, not by recurrence of RA-ILD. To the best of our knowledge, this is the first documentation of KL-6 elevation in serum in association with active MAC infection.No potential conflict of interest relevant to this article was reported.Biomed Central LtdActa Medica Okayama1465-993X142013Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responsesENHikariKogaNobuakiMiyaharaYasukoFuchimotoGenyoIkedaKoichiWasedaKatsuichiroOnoYasushiTanimotoMikioKataokaErwin W.GelfandMitsuneTanimotoArihikoKanehiroBackground: Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and challenged mice.
Methods: BALB/c mice were sensitized and challenged (primary) with ovalbumin (OVA). Six weeks later, a single OVA aerosol (secondary challenge) was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge.
Results: Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN) T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-beta 1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice.
Conclusion: These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the neutrophil elastase inhibitor reduced AHR to inhaled methacholine indicating the potential for its use as a modulator of the immune/inflammatory response in both the neutrophil-and eosinophil-dominant phases of the response to secondary allergen challenge.No potential conflict of interest relevant to this article was reported.Biomed Central LtdActa Medica Okayama1465-993X142013IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in miceENEtsukoKurimotoNobuakiMiyaharaArihikoKanehiroKoichiWasedaAkihikoTaniguchiGenyoIkedaHikariKogaHisakazuNishimoriYasushiTanimotoMikioKataokaYoichiroIwakuraErwin W.GelfandMitsuneTanimotoBackground: Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear.
Methods: In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid.
Results: Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment.
Conclusions: These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression.No potential conflict of interest relevant to this article was reported.